Watson-Crick Base-Pairing Properties of Nucleic Acid Analogues with Stereocontrolled and Torsion Angles (α,β-D-CNAs)

摘要

It is well-established that conformational restriction may lead to favorable complex formation because of an entropic advantage.[1] The concept of structural preorganization of oligonucleotides using conformationally restricted bicyclic nucleoside monomers was introduced more than ten years ago by Leumann and co-workers as a means of increasing duplex stability.[2], [3] Since then, mainly driven by the needs of antisense technology,[4] this concept has been widely evaluated by a number of research groups and has led to conformationally restricted oligomers with increased thermal duplex stabilities and improved biostability.[5]-[9] Without doubt, the most prominent examples of this class of compounds are locked nucleic acids (LNAs), in which the ribofuranose subunit is strictly locked into the 3-endo (N-type) conformation by a 2-O,4-C-methylene bridge.[10]-[13]